We have studied the IgG and IgM antibody responses to pneumococcal polysaccharides types 3 and 19 in eleven patients with active nephrotic syndrome and fifteen normal adult controls. Immunization in both patients with nephrotic syndrome and normal subjects resulted in significant increases in serum IgM antibody to types 3 and 19 pneumococcal polysaccharides. While controls also had a significant rise in IgG antibody to both types 3 and 19, patients with nephrotic syndrome had an increase in IgG antibody only to type 3. Also, after immunization, geometric mean titers of IgG antibodies to both types 3 and 19 were lower in patients with active nephrotic syndrome than in normal subjects (p less than 0.001). In patients with nephrotic syndrome, a significant correlation was found between serum albumin level and type 3 (p less than 0.01) and type 19 (p less than 0.05) antipneumococcal IgG antibody concentration. Furthermore, antipneumococcal IgG antibody was found in the urine of nephrotic patients, while no IgM antibody was excreted in the urine of nephrotic and adult controls. Our data demonstrate that patients with active nephrotic syndrome are able to mount a normal IgM immune response to pneumococcal polysaccharide antigens. The low IgG antibody levels are likely due to increased urinary losses and/or to a partial inability of these patients to produce IgG antibodies. Moreover, since protection may depend on antipneumococcal IgG antibody, these data raise questions as to the benefits of pneumococcal vaccination in patients with active nephrotic syndrome.